New compound ChlA-F induces autophagy-dependent anti-cancer effect via upregulating Sestrin-2 in human bladder cancer.
New compound ChlA-F induces autophagy-dependent anti-cancer effect via upregulating Sestrin-2 in human bladder cancer.
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DOI：
10.1016/j.canlet.2018.08.013
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发表时间：
2018-11-01
期刊：
影响因子：
9.7
通讯作者：
Huang C
中科院分区：
文献类型：
--
作者：
Hua X;Xu J;Deng X;Xu J;Li J;Zhu DQ;Zhu J;Jin H;Tian Z;Huang H;Zhao QS;Huang C
ChlA-F is a novel conformation-derivative of Cheliensisin A, styryl-lactone isolates that show potent anti-tumor potential in vivo and vitro. However, the anti-cancer activity and its potential mechanisms underlying ChlA-F action have never been explored. In the present study, we evaluated the potency of ChlA-F on autophagy-mediated anchorage-independent growth inhibition in human high-grade invasive bladder cancer (BC) cells. We found that ChlA-F treatment significantly inhibited anchorage-independent growth of human BC cells by inducing autophagy in a Sestrin-2 (SESN2)-dependent fashion. Our results revealed that ChlA-F treatment specifically induced SESN2 expression via increasing its transcription and mRNA stability. On one hand, ChlA-F treatment markedly attenuated Dicer protein abundance, in turn abolishing miR-27a maturation and further relieving miR-27a binding directly to SESN2 mRNA 3’UTR, thereby promoting SESN2 mRNA stabilization. On the other hand, ChlA-F treatment promoted Sp1 abundance and consequently mediated SESN2 transcription. These results demonstrate that its activation of the autophagic pathway through specifically promoting SESN2 expression mediates the anti-cancer effect of ChlA-F, which offers insights into the novel anti-cancer effect of ChlA-F on BC, as well as providing therapeutic alternatives against human BC.
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影响因子：
--
作者：
Jin H;Yu Y;Hu Y;Lu C;Li J;Gu J;Zhang L;Huang H;Zhang D;Wu XR;Gao J;Huang C
通讯作者：
Huang C
影响因子：
3.5
作者：
Fletcher, Claire E.;Dart, D. Alwyn;Bevan, Charlotte L.
通讯作者：
Bevan, Charlotte L.
影响因子：
4.8
作者：
Biggs, JR;Kudlow, JE;Kraft, AS
通讯作者：
Kraft, AS
影响因子：
3.6
作者：
Dickstein, Rian J.;Nitti, Giovanni;McConkey, David J.
通讯作者：
McConkey, David J.
影响因子：
11.2
作者：
Hu YL;Jahangiri A;Delay M;Aghi MK
通讯作者：
Aghi MK